Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

Reshef Tal,Richard V Grazi,Henry E Malter,David B Seifer

doi:10.1186/1477-7827-12-82

Reshef Tal, Richard V Grazi + Show 2 more

Open Access

https://doi.org/10.1186/1477-7827-12-82

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Abstract

BackgroundPolycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation.MethodsThis was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio.ResultsSerum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01).ConclusionsThese data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation.

Highlights

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity
No differences were observed between PCOS and non-PCOS women in serum levels of Placental growth factor (PlGF) at all three measured time points throughout controlled ovarian stimulation (Table 2)
No differences were noted between PCOS and non-PCOS women in sFlt-1 serum levels at all three measured time points throughout controlled ovarian stimulation (Table 3)

Summary

Introduction

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. SFlt-1, the soluble receptor for VEGF, has been shown to be decreased in serum of PCOS women undergoing controlled ovarian stimulation, contributing to increased VEGF bioavailability [15]. Several studies have demonstrated increased vascularity in the ovarian stroma of PCOS women as measured by Doppler blood flow velocities [13,16,17]. This increased ovarian vascularity was shown to correlate with increased serum VEGF levels in PCOS women [13,18], further supporting the notion that VEGF contributes to the vascular changes observed in PCO

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